Method and system for the diagnosis of disease using retinal image content and an archive of diagnosed human patient data

ABSTRACT

A method for diagnosing diseases having retinal manifestations including retinal pathologies includes the steps of providing a CBIR system including an archive of stored digital retinal photography images and diagnosed patient data corresponding to the retinal photography images, the stored images each indexed in a CBIR database using a plurality of feature vectors, the feature vectors corresponding to distinct descriptive characteristics of the stored images. A query image of the retina of a patient is obtained. Using image processing, regions or structures in the query image are identified. The regions or structures are then described using the plurality of feature vectors. At least one relevant stored image from the archive based on similarity to the regions or structures is retrieved, and an eye disease or a disease having retinal manifestations in the patient is diagnosed based on the diagnosed patient data associated with the relevant stored image(s).

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

The United States Government has rights in this invention pursuant tocontract no. DEAC05-00OR22725 between the United States Department ofEnergy and UT-Battelle, LLC.

CROSS-REFERENCE TO RELATED APPLICATIONS

N/A

FIELD OF THE INVENTION

The invention relates to automated methods for diagnosing retinalpathologies and other medical abnormalities.

BACKGROUND

The World Health Organization estimates that 135 million people havediabetes mellitus worldwide and that the number of people with diabeteswill increase to 300 million by the year 2025. More than 18 millionAmericans currently have diabetes and the number of adults with thedisease is projected to more than double by the year 2050. An additional16 million adults between the ages of 40-74 have pre-diabetes and are athigh risk for developing diabetes. Visual disability and blindness havea profound socioeconomic impact upon the diabetic population anddiabetic retinopathy (DR) is the leading cause of new blindness inworking-age adults in the industrialized world. The prevalence rates forDR and vision-threatening DR in adults over age 40 is 40.3% and 8.2%,respectively. It is estimated that as much as $167 million dollars and71,000-85,000 sight-years could be saved annually in the US alone withimproved screening methods for diabetic retinopathy.

The current methods used to address screening for DR relies on either apatient visit to a physician specifically trained to diagnose eyedisease from digital retinal photography, or the use of establishedretinal reading centers such as the Joslin Vision Network (Boston,Mass.), and Inoveon Corp. (Oklahoma City, Okla.). While reading centershave shown that digital photography is an effective tool for identifyingDR when performed by experienced, certified readers, the turn-aroundtime for a diagnosis is roughly 72 hours (3 days) on average. What isneeded is an automated diagnosis system that is self-contained andprovides very rapid turnaround, with minimal or no dependency on humaninterpreters.

SUMMARY OF THE INVENTION

A method for diagnosing medical conditions having retinal manifestationsincludes the steps of providing a content-based image retrieval (CBIR)system including an archive of stored digital retinal photography imagesand diagnosed patient data corresponding to the retinal photographyimages, the stored images each indexed in a CBIR database using aplurality of feature vectors, the feature vectors corresponding todistinct descriptive characteristics of the stored images. A query imageof the retina of a patient obtained. Using image processing, regions orstructures are then identified in the query image. The regions orstructures are described using the plurality of feature vectors. Atleast one relevant stored image from the archive based on similarity tothe regions or structures is identified. A disease having retinalmanifestations in the patient is then diagnosed based on the diagnosedpatient data associated with the retrieved relevant stored image(s).

The query image of the retina of the patient generally includes vasculararcades, the macula and optic disc, and surrounding regions. The regionsor structures identified using image processing preferably include bothnormal physiologic and anomalous pathologic regions or structures.

The medical conditions having retinal manifestations diagnosed cancomprises eye diseases, or a variety of non-eye disease which haveretinal manifestations. Eye diseases diagnosable using the inventioninclude, but are not limited to, common diseases of the optic nerve andmacula, such as glaucoma and age-related macular degeneration.

The anomalous regions can be selected based on one or more of spectralcontent, textures, structures, and shapes. The identifying step cancomprise imposing a macular coordinate system such that the spatialpositioning of disease-based morphological changes or location oflesions is described in relation to a position of the macula and theoptic disc. The database can include non-image data other than thediagnosed patient data, selected from the group consisting of age, race,gender, and medical history data for the patient.

The feature vectors are preferably indexed using an unsupervisedclustering method into a hierarchical search tree. Diagnosed patientdata can be provided by a retinal professional. The method can beentirely automatic. The obtaining step can comprise automaticallylocating the optic disc and macula regions, imposing a macularcoordinate system after automatic localization of a center of the maculain the image, and describing spatial positioning of disease-basedmorphological changes in relation to a position of the macula and opticdisc.

At least a portion of the digital retinal photography images comprisingthe archive can be obtained at a remote location. For example, theInternet can be used to provide digital retinal photography imagesobtained from the remote location.

In one embodiment of the invention, the method further comprises thestep of increasing information content for the CBIR database, whereinthe increasing information content step comprises the steps ofcalculating a visual similarity parameter value based on a degree ofvisual similarity between feature vectors of an incoming image beingconsidered for entry into the database and feature vectors of a mostsimilar of the plurality of stored images in the associated system, anddetermining whether to store or how long to store the feature vectorsassociated with the incoming image in the database based on the visualsimilarity parameter value. The visual similarity parameter can be basedon a Euclidean distance or an L-norm distance. The method can furthercomprise the step of defining a threshold value, wherein if the visualsimilarity parameter value is above the threshold value the featurevectors of the incoming image is denied entry into the database, and ifthe similarity parameter value is less than the threshold the featurevectors of the incoming image is entered into the database.

In one embodiment of the invention, the archive of digital retinalphotography images includes retinal images of the patient, the methodcomprising the steps of comparing the query image to retinal images ofthe patient in the archive, and assessing the progression of the diseasefor the patient.

A content-based image retrieval (CBIR) system for diagnosing diseaseshaving retinal manifestations comprises a computer apparatus programmedwith a routine set of instructions stored in a fixed medium, thecomputer apparatus comprising a CBIR database including a historicaldatabase comprising diagnosed patient data corresponding to an archiveof digital retinal photography images. The images are each indexed inthe database using a plurality of feature vectors, the feature vectorscorresponding to distinct descriptive characteristics of the images. Thesystem also includes structure for obtaining a query image of the retinaof a patient, structure to identify using image processing regions orstructures in the query image, structure for describing the regions orstructures using the plurality of feature vectors, structure forretrieving at least one relevant stored image from the archive based onsimilarity to the regions or structures, and structure for diagnosing adisease having retinal manifestations in the patient based on diagnosedpatient data associated with the relevant stored images. The systempreferably further comprises structure for implementing a clusteringmethod to index the feature vectors in a hierarchical search tree.

BRIEF DESCRIPTION OF THE DRAWINGS

A fuller understanding of the present invention and the features andbenefits thereof will be accomplished upon review of the followingdetailed description together with the accompanying drawings, in which:

FIG. 1 is a schematic representation of an exemplary computer-based CBIRsystem according to an embodiment of the invention.

FIG. 2 shows scanned images of a retina presented in three (3) differentlevels of diagnostic content. The diagnostic content in increasing orderis the red-free fundus imagery (top image), fluorescein angiographysequences (center images), and optical coherent tomography (OCT) retinalcross-sections (bottom image). Each successive mode of data, containsmore descriptive image content suitable for automated diagnosis, but ismore expensive and/or complex to gather.

FIG. 3 shows a scanned image of a retina showing its major structuresincluding macula and optic disc regions, as well as their relativescales.

FIG. 4 shows specific details of one embodiment of the invention showingthe inventive method comprising steps, steps 1 to 6.

DETAILED DESCRIPTION OF THE INVENTION

A method for diagnosing medical conditions having retinalmanifestations, including retinal pathologies, includes the steps ofproviding a content based image retrieval (CBIR) historical databaseincluding indexed retinal images and non-image data including diagnosedpatient data. CBIR generally refers to the field of study, methods, andtechnology used to index a large population of images so that they canbe ordered and retrieved based on visual content in an efficient manner.Visual content is typically described in terms of the color (i.e.,spectral content), textures, structures, and shapes of the imagery or ofparticular regions within the imagery. In a preferred embodiment,non-image data in addition to the diagnosed patient data correspondingeach image is provided, such as age, race, gender, and other medicalhistory data for the patient (or the family of the patient).

The images stored in the CBIR system are each indexed using a pluralityof feature vectors, the feature vectors corresponding to distinctdescriptive characteristics of the images. The feature vectors comprisethe indices for the images in the system. The feature vectors extractedfrom an image become the index for that image in the database, typicallybeing a unique identifier for that image. The indices are stored in atable in the CBIR database, usually along with a pointer to the locationof the image residing in a storage media (e.g. hard drive).

A query image of the retina of a patient for diagnosis is obtained thatgenerally includes the macula and optic disc, and surrounding regions.Using image processing normal physiologic and anomalous regions orstructures in the query image can be identified. The anomalous regionsare described using the plurality of feature vectors. Following a queryof the records stored in the database, at least one relevant storedimage is retrieved from the database based on similarity to theanomalous regions. A diagnosis for the patient for eye diseases andnon-eye diseases having retinal manifestations is then rendered based onthe diagnosed patient data associated with the relevant stored image(s).

The invention can be used to diagnose a variety of eye diseases. Eyediseases can include, but are not limited to, common diseases of theoptic nerve and macula, such as glaucoma and age-related maculardegeneration. However, the invention is not limited to diagnosing eyediseases since many non-eye diseases and medical conditions have retinalmanifestations.

Many systemic non-eye diseases have specific and significant retinalmanifestations. Such manifestations processed according to the inventioncan aid in the diagnosis, either alone, or in conjunction with othermeasurements. Examples of medical conditions having associated retinalmanifestations include hypertension, systemic vasculitides (such aslupus, oculo-arthropathies), coagulopathies, embolic diseases,infectious diseases of the blood and brain (endocarditis, toxoplasmosis,syphillis etc), leukemia, lymphoma and metastatic diseases to the eye,congenital malformations of the brain, genetic or acquired systemicdiseases that include ocular manifestations, such as von Hippel Lindauor tuberous sclerosis.

FIG. 1 illustrates a diagnostic CBIR system 1 in accordance with oneinventive arrangement. The diagnostic CBIR system 1 includes storagemedia 9 having stored therein a collection of retinal images indexed asfeature vectors in associated feature vector list 7 which storesdescriptive data corresponding to each stored image. System 1 alsopreferably includes non-image storage 12 for storing non-imageinformation comprising diagnosed patient data, along other non-imagedata, such as age, race, gender, and other medical history data for thepatient (or history of the family of the patient).

System 1 includes three basic modules, an image feature extractionmodule 2, an indexing module 3, and a querying module 4, with eachmodule performing a different CBIR function.

First, the image feature extraction module 2 can represent query imageand database images 8 in terms of a small number of numericaldescriptors. Specifically, the image feature extraction module 2 canreceive as an input, retinal image 8. The image feature extractionmodule 2 can survey the image 8 deriving a vector of numericaldescriptors corresponding to the image 8. In a preferred embodiment asdisclosed in U.S. Pat. No. 6,751,343 to Ferrel et al entitled “Methodfor indexing and retrieving manufacturing-specific digital imagery basedon image content”, unlike prior CBIR systems, the manufacturing imagerycan be described in terms of a plurality of independent sets ofcharacteristics, such as image modality and overall characteristics,substrate-background characteristics, and anomaly-defectcharacteristics. Ferrel et al. is incorporated by reference into thepresent application in its entirety.

Moreover, the characteristics used to describe the modality, background,and defect are based on the texture, color, and shape of the image orimage structures. In a retinal diagnostics embodiment thesecharacteristics describe modality, physiologic structure such as thecharacteristics of the optic nerve, macula region and vascular arcades,and the structures associated with pathology from lesions, hemorrhages,and edema. In the preferred embodiment, the image feature extractionmodule 2 pre-processes every image to generate a series of featurevectors having these descriptive set of features, each vector weightedto a particular characteristic of the stored image. Subsequently, theimage feature extraction module 2 can store each of the series ofvectors in a corresponding feature vector list 7.

The second module forming the diagnostic CBIR system 1, an indexingmodule 3, can generate a series of hierarchical search trees to generatean hierarchical search/indexing tree 6, each binary search hierarchicalsearch tree corresponding to a particular characteristic of a storedimage. Specifically, the indexing module 3 can read a vector ofnumerical descriptors contained in a particular feature vector list 7,the vector corresponding to a stored image. Subsequently, preferablyusing an unsupervised clustering method, the indexing module 3 cancreate and insert a node containing the vector into a hierarchicalsearch tree 6 keyed on the same image characteristic as the featurevector list 7. The indexing module 3 can perform the node insertionoperation for each feature vector list 7 stored. Thus, each resultinghierarchical search tree 6 can provide for the rapid location ofcandidate imagery stored in storage media 9, each hierarchical searchtree 6 weighted to a particular image characteristic.

The third module forming the diagnostic CBIR system 1, a querying module4, can accept a query image from a user and can return to the user, acollection of similar images stored in storage media 9. Specifically,the querying module 4 can perform an appropriate first level datareduction based upon the query image's associated vectors.Significantly, the image feature extraction module 2, using the queryimage as an input, can generate the associated feature vectors. Usingthe feature vector numerical descriptors as a guideline, a very rapidtraversal of indexing tree 6 in the first-level data reduction routinecan produce a preliminary selection of matching images stored in storagemedia 9. Subsequently, a relevance feedback routine contained within thequerying module 4 can receive input from the user to further focus theimage search to the most relevant images. In particular, in a preferredembodiment the user can select several images contained in thepreliminary selection of matching images, the selected images havingsimilar characteristics to the query image. Following the relevancefeedback procedure, a second level data reduction can be performed usingthe relevance feedback. Once the system has produced a reduced set ofimage descriptions, each image can be combined to provide the user ofsystem 1 with a vastly reduced set of images having similarcharacteristics to the query image.

Although the present invention shares certain basic details with Ferrelet al., there are significant and non-obvious details specific to theimplementation of the present invention that are unique to DR. Forexample, the methods for extracting retinal structures, such as theoptic nerve, macula, vasculature, and the variety of lesions present,and for describing these structures, such as the statistical featuresused, are very different from the semiconductor or othermanufacturing-based defect case disclosed in Ferrel et al. Also, thepresent invention uses non-image derived data, such as disease states toautomatically infer and present a description of pathology to the user.In one embodiment the disease states are put forth by the PreferredPractice Patterns of the American Academy of Opthalmology (AAO, 2003),the disease states are assigned by a retinal professional (expert), suchas an opthalmologist, and stored along with the historical retinal imagedatabase.

The computer diagnosis method according to the invention is generallyimplemented on a high speed computer system. The system includes memory(preferably non-volatile memory) which stores the historical databasecontaining diagnosed patient data in a large archive of digital retinalphotography.

FIG. 2 shows scanned images of a retina presented in three (3) differentlevels of diagnostic content. The exemplary diagnostic content is inincreasing order the red-free fundus imagery (top image), fluoresceinangiography sequences (center images), and optical coherent tomography(OCT) retinal cross sections (bottom image). As noted above, the retinalimage data associated with the patient is preferably stored alongnon-image data, comprising diagnostic data and other non-image dataincluding age, race, gender, and other medical history data for thepatient. Each patient's record diagnostic data record stored in thearchive preferably includes a description of the prevalent pathology attwo levels, such as the two levels described below.

In a preferred embodiment, the record contains a general two levelcharacterization of the disease state, such as put forth by thePreferred Practice Patterns of the American Academy of Opthalmology(AAO, 2003) as follows:

1. No Retinopathy

2. Mild Retinopathy

3. Moderate Retinopathy

4. Moderate to Severe Retinopathy

5. Severe Retinopathy

6. Proliferative Retinopathy

The patient record preferably also has a further detailed description oftheir particular pathology according to:

Presence of neovascular variation of the optic disc,

Presence of microaneurysms and retinal hemorrhages,

Presence of drusen,

Presence of exudates,

Presence of cotton-wool spots, and,

the locations of these events relative to the fovea and optic nerve.

In addition,

-   -   Presence or absence of clinically significant macular edema and        its size and location relative to the fovea (of significance in        assessing the severity of disease and risk of vision loss in        each eye).

FIG. 3 shows a scanned image of a retina showing major structuresincluding macula and optic disc regions, as well as their relativegeometric scales. As described earlier, the invention operates byanalyzing and identifying, through image processing, critical structuresof the retina that include and surround the macula and optic discregions. Morphological or pigmentation changes in these regions, alongwith the presence of lesions such as drusen, exudates, dot hemorrhages,cotton wool spots, etc., have been found to be key indicators of theonset or progression of blinding eye disease. The computer analysismethod further describes these regions and structures according a seriesof statistical feature vectors. These feature vectors are used to indexthe patient data in the CBIR system.

The CBIR aspects of the present invention only generally require that atleast one image (more generally a plurality of images) with similarvisual characteristics to that of an undiagnosed query image be found inthe archive. Automated diagnosis according to the invention is madepossible based on the finding that a similar process or phenomena likelygenerates images that are visually similar. This principle is appliedherein to medical diagnostics of retinal imagery. The diagnosis is thusmade indirectly based on the characterization of disease in theretrieved population (from the archive) according defined categories,such as the two level categories provided above.

Specific details of one embodiment of the invention is provided in FIG.4. The method is shown as comprising six steps, steps 1 to 6.

Step 1. A digital retinal image is collected from a patient andautomatically characterized to locate the vascular arcades, optic discand macula regions. From this characterization, a macular coordinatesystem is imposed 21 such that the spatial positioning of disease-basedmorphological changes, location of lesions, etc., can be described inrelation to the position of the macula and optic disc.

Step 2. Statistical features (shown as feature vectors, f₀ to f_(N).)are extracted 22 from the salient regions of the retina which describe:(a) detected lesions such as drusen, exudates, cotton wool spots, dothemorrhages, etc., (b) lesion statistics by category, e.g., moments,total counts, radial or annular distributions surrounding the maculacenter, etc., (c) oriented textures from the macula region, e.g., Gaboror Wald features, etc, and (d) features of the vascular arcade thatdescribe shape, density, symmetry, etc.

Step 3. Apply principle component analysis (PCA) and linear discriminantanalysis (LDA) to provide a mapping from a large feature vector set to ashort, directed feature vector set 23. PCA and LDA methods are used toincrease the discriminating power of a reduced feature set whilemitigating feature redundancy, noise, and length. This step provides fora simplified content-based indexing architecture that allows images tobe described in terms of the image content represented by an exemplarlibrary, as opposed to the potentially complex feature structure used torepresent the original images. By applying the PCA/LDA method, it is notuncommon to map an extensive feature set (e.g., >500 features) to a verysuccinct and discriminating subset (e.g., <50 features). Thisreduced-length feature vector becomes the index for each image in thedatabase. This results in a more efficient Approximate Nearest Neighbor(ANN) search process in terms of both retrieval performance (e.g.,precision) and the speed of retrieval.

In adapting the directed indexing method to retinal diagnostics, theuser generally defines a directed indexing library (DIL) that containsexemplars of different categories of disease or that represent thevariation of pathology associated with a particular disease state. Forexample, a DIL may be constructed that contains examples of early phasebackground DR as one category, proliferative DR as another category,age-related macular degeneration as another, and cystoid macular edemaas yet another category. Each row of the DIL will contain examples ofeach particular category of interest. This will be established prior tobuilding an indexing structure for the diagnostic CBIR system. The DILwill then be used to map the high-dimensional features of the originalimage regions to a lower dimensional feature space that focuses on theproblem of retinal pathology characterization. The derived featuremapping is then applied to all future image content that enters thesystem. This method provides a method of mapping user semantics (i.e.,meaning in the data) to the extracted features therefore matching userexpectations to retrieval and therefore diagnostic performance, i.e.,mitigating the semantic gap issue in CBIR systems.

Step 4. Using the CBIR method disclosed in U.S. Pat. No. 6,535,776 toTobin, Jr. entitled “Method for localizing and isolating an errantprocess step”, an indexing tree is built 24 with an Approximate NearestNeighbor (ANN) method for efficient retrievals using the reduced featurevector for each patient record stored in the archive.

Step 5. Retrievals are then performed by formulating a query with anundiagnosed patient 25. The query is submitted to the CBIR system and apopulation of N visually similar images are returned, where N is adynamic number ≧1 determined by establishing a similarity threshold, T,using a suitable similarity metric (e.g., the population of images i=1,2, . . . N, for which similarity is ˜T). In the embodiment used ininitial tests performed, the metric, Si(Q,v_(i))=1−d(Q,v_(i))√M, where Mis the number of features used (i.e., the dimension of the featurespace) to describe the retinal imagery and i=1, 2, . . . N, being thesize of the population of visually similar images for which Si(Q,)˜T,and d(Q,v_(i)) is a Euclidean of generalized L-norm distance function.

Step 6. Once a population of visually similar image data is returnedcontaining N records, a statistical analysis is performed on the entirepopulation or a sub-population to determine the prevalence of variousdisease states based on the frequency of occurrence 26. Subpopulationscan be formed according to the patient gender, race, age, or othermedical facts stored in the database archive. It is important that alarge population of diagnosed and indexed patient data exist in theimage archive to ensure statistical significance and uniformity acrossthe registered disease types, gender, race, age, etc., in the system.Automatically performing a medical diagnosis based on a data archiveattached to a content-based indexing of a large human patient populationis a unique attribute of the present invention.

The invention can also be used to assess progression of retinal diseaseor diseases having retinal ramifications in a specific patient over aperiod time. As described above, The general CBIR method according tothe invention permits evaluation of disease state using an archive ofstored images with associated diagnosis and assessing the relativesimilarity of an unknown image to that library of images to obtain adiagnosis. However, once established as a population screening tool, thedatabase, such as a Health Insurance Portability and Accountability Act(HIPAA) compliant database, of images from each patient can beestablished and the CBIR algorithm can be used to find and compare aretinal image to an image taken of the eye(s) of the same patient at oneor more earlier points in time (e.g. years before). This embodimentprovides assessment of progression of disease for patients as well asdisease status relative to the archive.

For a very large patient population, as would be expected to bedeveloped over a long time period from multiple sources of input such asthrough a web-based national subscription and submission system, itwould be advantageous to reduce redundancy of image content in thedatabase. For this purpose, an indexed data library that minimizesredundancy and provides a more uniform distribution of patient caseswould be desirable.

In one embodiment, a method of increasing information content forcontent-based image retrieval (CBIR) systems comprises the step ofproviding a CBIR database, the database comprising an index for aplurality of stored digital images using a plurality of feature vectors.The feature vectors correspond to distinct descriptive characteristicsof the images. A visual similarity parameter value is calculated basedon a degree of visual similarity between feature vectors of an incomingimage being considered for indexing into the database and featurevectors associated with a most similar of the images stored in theassociated system. Based on the calculated visual similarity parametervalue, it is determined whether to store or how long to store thefeature vectors of the incoming image in the database.

The visual similarity parameter can be based on a distance, divergenceor other information-theoretical comparison. Distances can includeMinkowski-form distances, such as Euclidean or L-norm, or Mahalanobis orquadradic form distance. The divergences can include a Kullback-Leiberor Jeffrey divergence. In a preferred embodiment, the method furthercomprises the step of defining a threshold value, wherein if the visualsimilarity parameter value is above the threshold value the featurevectors associated with the incoming image is denied entry into thedatabase, and if the similarity parameter value is less than thethreshold the feature vectors of the incoming image is entered into thedatabase. A plurality of threshold values can be defined, wherein theplurality of threshold values are used to define ranges of thesimilarity parameter values which are paired with durations for storagelifetimes in the database for the feature vectors of the incoming image.

Principal benefits of the present invention include the following:

-   -   1. A method for rapidly and automatically analyzing retinal        imagery to provide a reliable diagnosis in a fraction of the        time required by the reading center model currently in use in        2006.    -   2. An ability to provide an inexpensive, high-throughput retina        analysis (and diseases having retinal manifestations) and        diagnosis method and system for use in rural areas throughout        the world (including the U.S. and in third-world countries)        where medical opthalmology and other health care expertise is        limited.    -   3. A method for making productive use of the historical record        of digital fundus imagery that is being collected by the medical        community today including red-free fundus imagery, imagery        collected by non-mydriatic cameras, fluorescein angiography, and        optical coherence tomography.    -   4. A method to provide the large organizations, such as the U.S.        military, with the capability to perform rapid and accurate near        real-time retinal scans on large numbers of personnel. In the        case of the U.S. military, the invention can be used for        personal in the service (e.g., abroad) and through the Veterans        Administration with highly efficient throughput.

As noted above, although described relative to diagnosing retinalpathologies, the invention can be applied to other automated diagnosisscenarios based on other modes of biomedical imagery. For example, theinvention can be used in conjunction with various imaging modalitiesincluding computed tomography (CT), positron emission CT (PET), singlephoton emission CT (SPECT), magnetic resonance imaging (MRI), andcellular oncology. The invention thus can be used to detect a broadrange of diseases and abnormalities including various forms of cancer.

It is to be understood that while the invention has been described inconjunction with the preferred specific embodiments thereof, that theforegoing description as well as the examples which follow are intendedto illustrate and not limit the scope of the invention. Other aspects,advantages and modifications within the scope of the invention will beapparent to those skilled in the art to which the invention pertains.

1. A method for diagnosing medical conditions having retinalmanifestations, comprising the steps of: providing a CBIR systemincluding an archive of stored digital retinal photography images anddiagnosed patient data corresponding to said retinal photography images,said stored images each indexed in a CBIR database using a plurality offeature vectors, said feature vectors corresponding to distinctdescriptive characteristics of said stored images, and said diagnosedpatient data identifying at least one of a plurality of disease statesand one of one or more severity levels for the one of the plurality ofdisease states; obtaining a query image of the retina of a patient;identifying using image processing a plurality of separate regions orstructures in said query image; describing said regions or structuresusing said plurality of feature vectors; retrieving a population ofstored images from said database based on similarity to said regions orstructures, and diagnosing a disease having retinal manifestations insaid patient by: statistically analyzing said diagnosed patient data forsaid population to determine ones of the plurality of disease stated insaid population and a prevalence of the ones of the severity levelscorresponding to the ones of the plurality of disease states in saidpopulation, determining the absence or presence of a disease state inthe patient based on the ones of the plurality of disease states in saidpopulation, and, if a disease state is present in the patient, aseverity level of the disease state present in the patient based atleast on a prevalent one of the severity levels corresponding to theones of the plurality of disease states in the population associatedwith the present disease state.
 2. The method of claim 1, wherein saidregions or structures include normal physiologic and anomalouspathologic regions or structures.
 3. The method of claim 2, wherein saidanomalous regions are selected on the basis of spectral content,textures, structures, or shapes.
 4. The method of claim 1, wherein saidquery image includes vascular arcades, macula, and optic disc andsurrounding regions.
 5. The method of claim 4, wherein said identifyingstep comprises imposing a macular coordinate system such that thespatial positioning of disease-based morphological changes or locationof lesions is described in relation to a position of said macula andsaid optic disc.
 6. The method of claim 4, wherein said obtaining stepcomprises: automatically locating said optic disc and said macularegions; imposing a macular coordinate system after automaticlocalization of center of said macula in said image, and describingspatial positioning of disease-based morphological changes in relationto a position of said macula and said optic disc.
 7. The method of claim1, wherein said database includes non-image data other than saiddiagnosed patient data, selected from the group consisting of age, race,gender, and medical history data for said patient.
 8. The method ofclaim 1, wherein said feature vectors are indexed using an unsupervisedclustering method into a hierarchical search tree.
 9. The method ofclaim 1, wherein said diagnosed patient data is provided by a retinalprofessional.
 10. The method of claim 1, wherein said method is entirelyautomatic.
 11. The method of claim 1, wherein at least a portion of saiddigital retinal photography images are obtained at a remote location.12. The method of claim 1, further comprising the step of increasinginformation content for said system, wherein said increasing informationcontent comprises the steps of: calculating a visual similarityparameter value based on a degree of visual similarity between featuresvectors of an incoming image being considered for entry into saiddatabase and feature vectors of a most similar of said plurality ofstored images in said database, and determining whether to store or howlong to store said feature vectors associated with said incoming imagein said database based on said visual similarity parameter value. 13.The method of claim 12, wherein said visual similarity parameter isbased on a Euclidean distance or an L-norm distance.
 14. The method ofclaim 12, further comprising the step of defining a threshold value,wherein: if said visual similarity parameter value is above saidthreshold value said incoming image is denied entry into said database,and if said similarity parameter value is less than said threshold saidincoming image is entered into said database.
 15. The method of claim 1,wherein said disease comprises an eye-disease.
 16. The method of claim1, wherein said disease comprises a non-eye disease.
 17. The method ofclaim 1, wherein said archive of digital retinal photography imagesincludes retinal images of said patient, wherein said method comprisesthe steps of: comparing said query image to retinal images of saidpatient in said archive, and assessing the progression of said diseasefor said patient.
 18. The method of claim 1, wherein said statisticaldetermination includes identifying a sub-population of said populationbased on one or more of patient gender, race or age.
 19. A system fordiagnosing diseases having retinal manifestations, comprising: computerapparatus programmed with a routine set of instructions stored in afixed medium, said computer apparatus comprising: a CBIR systemincluding an archive of stored digital retinal photography images anddiagnosed patient data corresponding to said retinal photography images,said stored images each indexed in a CBIR database using a plurality offeature vectors, said feature vectors corresponding to distinctdescriptive characteristics of said stored images, and said diagnosedpatient data identifying at least one of a plurality of disease statesand one of one or more severity levels for the one of the plurality ofdisease states; structure for obtaining a query image of the retina of apatient; structure for identifying using image processing a plurality ofseparate regions or structures in said query image; structure fordescribing said regions or structures using said plurality of featurevectors; structure for retrieving a population of stored images fromsaid archive based on similarity to said regions or structures, andstructure for diagnosing a disease having retinal manifestations in saidpatient by: statistically analyzing said diagnosed patient data for saidpopulation to determine ones of the plurality of disease states in saidpopulation and a prevalence of the ones of the severity levelscorresponding to the ones of the plurality of disease states in saidpopulation, determining the absence or presence of a disease state inthe patient based on the ones of the plurality of disease states in saidpopulation, and, if a disease state is present in the patient, aseverity level of the disease state present in the patient based atleast on a prevalent one of the severity levels corresponding to theones of the plurality of disease states in the population associatedwith the present disease state.
 20. The system of claim 19, furthercomprising structure for implementing a clustering method to index saidat least one feature vector in a hierarchical search tree.